All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis.
Publication/Presentation Date
4-13-2024
Abstract
Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes. Restorative retinoic acid therapy in murine glioma models promotes clonal CD4
ISSN
2692-8205
Published In/Presented At
Rao, A., Zhang, X., Cillo, A. R., Sussman, J. H., Sandlesh, P., Tarbay, A. C., Mallela, A. N., Cardello, C., Krueger, K., Xu, J., Li, A., Xu, J., Patterson, J., Akca, E., Angione, A., Jaman, E., Kim, W. J., Allen, J., Venketeswaran, A., Zinn, P. O., … Amankulor, N. M. (2024). All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis. bioRxiv : the preprint server for biology, 2024.04.09.588752. https://doi.org/10.1101/2024.04.09.588752
Disciplines
Medicine and Health Sciences
PubMedID
38645178
Department(s)
Department of Surgery
Document Type
Article